Many studies on neoplastic transformation and tumor progression focused and still focus on tumor cells. However, one important aspect in tumor progression is the interaction between cancer cells and the stromal microenvironment [1]. The stroma was initially thought to have only supportive function in tumor development, but there is increasing evidence that stromal components actively take part in tumor progression and, therefore, are major players in tumor invasion [2-4]. Beside inflammatory and endothelial cells another crucial cellular component of the stroma is the myofibroblast (MF), a modulated fibroblast which has acquired the capacity to express the biomarker alpha-smooth muscle actin (αSMA) [5]. Myofibroblasts remodel the connective tissue during wound healing, but also interact with cancer cells at all stages of tumor progression and may thus control such phenomena as tumor invasion and angiogenesis [6].
Although it is known that reactive oxygen species (ROS) can be key regulators at all stages of cancer development [7], the molecular mechanisms underlying the ROS-dependent tumor-stroma interaction in tumor progression and its potential therapeutic modulation to prevent tumor invasion have not been fully elucidated until recently. A better understanding of the ROS initiated molecular mechanisms mediating interaction between the tumor and the tumor microenvironment would be helpful for the development of novel therapeutic strategies, as invasion and metastases are the most common problems in cancer therapy.
Nanomedicine, the medical application of nanotechnology, deals with the application of structures of the size 100 nanometers or smaller in at least one dimension and seeks to deliver a valuable set of research tools and clinically helpful devices in the near future [8]. The small size of nanoparticles endows them with properties that can be very useful in carcinogenesis, particularly in imaging and anti-cancer therapy. A nanoparticle-based therapeutic approach may have the potential as supplementation therapy supporting the classical anticancer strategies such as radiation or the use of anticancer drugs. If future studies show that a nanoparticle-based anticancer therapy has less harmful effects, it is aimed for the application of nanoparticles as major anticancer approach. In both cases, the treatment with nanoparticles should result in killing tumor cells or in prevention of tumor invasion while leaving normal healthy cells intact.
In that context, nano-sized magnetic iron particles are increasingly being used in cancer therapy. Once uptaken by tumor cells, such particles can be magnetically heated leading to localized cell death while healthy cells remain alive [9,10]. Free oxygen radicals generated by exposure to cerium oxide nanoparticles (CNP) produced significant oxidative stress, which killed lung carcinoma cells [11]. However, the toxicity of CNP is still controversial as an antioxidant function of CNP is described as well. Vacancy engineered CNP exhibited superoxide dismutase mimetic activity in human epidermal keratinocytes [12] and in a cell-free test tube system [13].